Effect of Long-Term Mesalamine Therapy on Cancer-Associated Gene Expression in Colonic Mucosa of Patients with Ulcerative Colitis.

Abstract:

BACKGROUND:The role of 5-aminosalicylic acid (5-ASA or mesalamine) in the prevention of colorectal cancer in ulcerative colitis (UC) patients was reported, but the effect on molecular targets in UC colon mucosa is unknown. AIM:This observational study evaluates gene expression levels of 5-ASA targets using serial colon biopsy specimens from UC patients undergoing long-term 5-ASA therapy. METHODS:Transcript levels were compared between colonoscopic biopsy specimens collected from 62 patients at initial and final follow-up colonoscopy at 2-6 years. All patients had mild-to-moderate UC and were undergoing long-term 5-ASA maintenance. Stepwise multiple linear regression analyses were performed to correlate changes in transcript levels with therapeutic response (Mayo clinical score endoscopy and DAI and/or Nancy histopathology score) and nonclinical variables. RESULTS:The transcript levels of colorectal carcinogenesis-associated known 5-ASA target genes were significantly reduced after prolonged 5-ASA therapy (P < 0.005-0.03). Multiple linear regression models predicted significant association between transcript levels of Ki-67, NF-kB (p65), PPARγ, COX-2 and IL-8, CDC25A, and CXCL10 with duration of drug (5-ASA) exposure (P ≤ 0.05). Ki-67, NF-kB (p65), and CXCL10 transcripts were also correlated with reduced endoscopy sub-score (P ≤ 0.05). COX-2, IL-8, CDC25A, and TNF transcripts strongly correlated with DAI sub-scores (P ≤ 0.05). Only COX-2 and IL-8 transcript levels correlated (P ≤ 0.05) with Nancy histological score. CONCLUSION:This study provides molecular evidence of changes in carcinogenesis-related targets/pathways in colon tissue during long-term 5-ASA maintenance therapy that may contribute to the observed chemopreventive effects of 5-ASA in UC patients.

journal_name

Dig Dis Sci

authors

Bajpai M,Seril DN,Van Gurp J,Geng X,Alvarez J,Minacapelli CD,Gorin S,Das KK,Poplin E,Cheng J,Amenta PS,Das KM

doi

10.1007/s10620-018-5378-8

subject

Has Abstract

pub_date

2019-03-01 00:00:00

pages

740-750

issue

3

eissn

0163-2116

issn

1573-2568

pii

10.1007/s10620-018-5378-8

journal_volume

64

pub_type

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